METTL3-Mediated m6A Modification of LINC00839 Maintains Glioma Stem Cells and Radiation Resistance by Activating Wnt/β-Catenin Signaling

Authors

Jianxing Yin
Fangshu Ding
Zhangchun Cheng
Xin Ge
Yanhui Li
Ailiang Zeng
Junxia Zhang
Wei Yan
Zhumei Shi
Xu Qian
Yongping You
Zhiliang Ding
Jing Ji
Xiefeng Wang

Publication Date

7-12-2023

Journal

Cell Death & Disease

Abstract

Long noncoding RNAs (lncRNAs) are involved in glioma initiation and progression. Glioma stem cells (GSCs) are essential for tumor initiation, maintenance, and therapeutic resistance. However, the biological functions and underlying mechanisms of lncRNAs in GSCs remain poorly understood. Here, we identified that LINC00839 was overexpressed in GSCs. A high level of LINC00839 was associated with GBM progression and radiation resistance. METTL3-mediated m6A modification on LINC00839 enhanced its expression in a YTHDF2-dependent manner. Mechanistically, LINC00839 functioned as a scaffold promoting c-Src-mediated phosphorylation of β-catenin, thereby inducing Wnt/β-catenin activation. Combinational use of celecoxib, an inhibitor of Wnt/β-catenin signaling, greatly sensitized GSCs to radiation. Taken together, our results showed that LINC00839, modified by METTL3-mediated m6A, exerts tumor progression and radiation resistance by activating Wnt/β-catenin signaling.

Keywords

Humans, beta Catenin, Cell Transformation, Neoplastic, Glioma, Methyltransferases, Neoplastic Stem Cells, RNA, Long Noncoding, Wnt Signaling Pathway, CNS cancer, Long non-coding RNAs, CNS cancer, Long non-coding RNAs

DOI

10.1038/s41419-023-05933-7

PMID

37438359

PMCID

PMC10338500

PubMedCentral® Posted Date

7-12-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes